ODP227 Nivolumab Induced Type 1 Diabetes

INTRODUCTION: Nivolumab is a treatment option used for renal cell carcinoma (RCC). It is reported to have high response rate to renal cancer cells with rare adverse events to the endocrine system including type 1 diabetes mellitus (DM1). Our case reports the use of nivolumab and ipilimumab in a patient with RCC with timeline of hyperglycemia following initiation of the regimen. CLINICAL CASE: A 71-year-old woman with RCC metastasized to the lungs experienced adverse effects leading discontinued sunitinib therapy. Her imaging showed increased pulmonary nodules with tumor extension into left superior and inferior pulmonary veins. Therapy with Ipilimumab 56 mg plus nivolumab 169 mg initiated shortly. Pre-treatment labs were within normal limits. Labs remained within normal limits (plasma glucose 82 mg/dL) before second treatment. Less than a week following 2 nd treatment, she presented with generalized rash and was sent to the emergency room (ER). She was treated with one dose IV and a course of PO steroids for total 5 days. Infusions were put on hold. Despite rash resolving, she continued to have low-grade fever (99.1°F). She also reported 10 lbs. weight loss and polydipsia. Three weeks follow-up lab noted plasma glucose level of 559 mg/dL. She was instructed to go to the ER. ER labs: HbA1c: 9.1%,, plasma glucose 525 mg/dL, B-hydroxybutyrate 10.47 mmol/L; UA 3+ glucose; 2+ ketones. She met criteria for diabetes ketoacidosis (DKA). She was admitted, started and later discharged on insulin therapy with referral to see outpatient diabetes providers. Labs obtained during outpatient follow up include: C-peptide 0.3 ng/ml & paired plasma glucose of 246 mg/dl. Nivolumab monotherapy re-initiated later. With insulin therapy, HbA1c improved with most recent HbA1c at 7.7%. Clinical Lesson: There is evidence of anti-PD-1-monoclonal-antibody-induced diabetes mellitus throughreduced activity of PD-1 which is common to both traditional onset type 1 diabetes or antiPD-1 therapy-related diabetes. PD-1 reduction may cause inappropriate activation of T cells causing autoimmune response against pancreatic beta cells. Clotman et al reports 42 cases of PD-1 inhibitor–induced DM1. Half of tested case subjects (22/39 or 56%) had detectable diabetes-related autoantibodies; however, no clear pattern of diabetes-related autoantibodies. Additionally, median interval from immunotherapy initiation to diagnosis of diabetes was 5 weeks in GADA-positive subjects vs 9 weeks in GADA negative subjects. Li Zhang et al reports 735 cases of immune checkpoint inhibitors (ICI) DM: 25% presented fulminant DM1; 45% presented in DKA. Of these, 25% had severe case and 5.5% resulted in deaths. Because immunotherapy use will continue to increase, raising awareness of ICI DM induced by anti–PD-1 therapy is essential. Although incident is rare, missing or delaying diagnosis can not only significantly impact a patient's life but be potentially life-threatening. Presentation: No date and time listed